17 Under these conditions, and using multiple induction tetani, LTP has been observed to last for a year in rats. 15, 16 Experiments in intact animals allow for assessment of the longevity of LTP in the hippocampus using chronically implanted recording and stimulating electrodes. Later it was found that low frequency trains of electrical stimulation (1 Hz) can induce LTD in hippocampal and cortical pathways. Subsequent studies have been almost exclusively conducted on rats and mice. Recordings of the synaptic response (the population EPSP) evoked in the population of activated granule cells revealed a lasting enhancement of synaptic strength following tetanic (high frequency) stimulation.
1 In this study, LTP was induced using a stimulating electrode to induce a brief high-frequency train of action potentials in the afferent pathway, thereby ensuring coincident pre- and post-synaptic depolarization. LTP was originally observed in vivo in the hippocampus of anaesthetized rabbits at synapses between the medial perforant path and granule cells of the dentate gyrus. As a framework for this discussion we will first provide some background on LTP and LTD. In this review we will discuss clinical applications of LTP, LTD and related forms of synaptic plasticity and the technologies that may allow the erasure and induction of changes in synaptic strength in the human CNS. Manipulation of synaptic strength using various developing technologies may provide a means of normalizing synaptic strength and thereby ameliorating plasticity-related disorders of the CNS. A variety of neurological conditions arise from lost or excessive synaptic drive due to sensory deprivation during childhood, brain damage or disease. LTP and LTD have another potentially important role in modern neuroscience, and that is the possibility that they may be exploited to treat disorder and disease in the human central nervous system (CNS). 7- 13 The debate on the relevance of LTP and LTD to human memory will in all likelihood continue until we can harness these processes to mimic the formation of a memory without prior experience. In addition, it has been demonstrated that LTP- and LTD-like changes in synaptic strength occur as a memory is formed at various sets of synapses in the brain, and that these changes can occlude the artificial induction of LTP and can be occluded by the prior induction of LTP. 5, 6 However, at the molecular level, it is very clear that LTP/LTD and many forms of memory rely upon similar molecular mechanisms. 3, 4 Whether LTP and LTD are the actual synaptic processes underlying learning and memory, as most neuroscientists believe, has not yet been definitively resolved. The complementary process of long-term depression (LTD), in which the efficacy of synaptic transmission is reduced, shares these characteristics and has also received much attention as a candidate mnemonic process. 2 Notably, LTP is long-lasting and input-specific (changes can be induced at one set of synapses on a cell without affecting other synapses).
LTP has been a source of great fascination to neuroscientists since its discovery in the early 1970′s 1 because it satisfies criteria proposed by Donald Hebb for a synaptic memory mechanism in his influential book ‘The Organization of Behavior'. Long-term potentiation (LTP) is a form of activity-dependent plasticity which results in a persistent enhancement of synaptic transmission. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.
Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive.
A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system.